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Hemofiltrability of H 2 ‐Receptor Antagonist, Famotidine, in Renal Failure Patients
Author(s) -
Saima Shigeki,
Echizen Hirotoshi,
Yoshimoto Keiko,
Ishizaki Takashi
Publication year - 1990
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1990.tb03456.x
Subject(s) - hemofiltration , ultrafiltration (renal) , famotidine , renal function , chromatography , filtration (mathematics) , chemistry , urology , hemodialysis , medicine , surgery , pharmacology , mathematics , statistics
To determine if a new H 2 ‐receptor antagonist, famotidine, would be significantly removed by arteriovenous hemofiltration, we measured plasma concentrations and amounts of the drug recovered in ultrafiltrate during 18 sessions of an intermittent hemofiltration performed in five patients with renal failure receiving the repeated intravenous dosings of the drug (5–20 mg/day). Plasma and ultrafiltrate drug concentrations were determined by using a high performance liquid chromatography with fluorescent detection. The mean (±SD) amount of the drug removed by the procedure, which was performed at the mean ultrafiltration rate of 19.0 ± 6.0 ml/min over the mean duration of 212 ± 168 min, corresponded to 4.1 ± 2.2% of the daily maintenance doses. There was a significant (r = 0.90, P < .01) linear relationship between the hemofiltration clearance and the ultrafiltration rate, indicating that the sieving coefficient, an index of filtration efficiency, for the drug was largely constant (i.e., 0.73 ± 0.10) over the ranging filtration rates (i.e., 3.9–29.5 mL/min) employed in the present study. When the mean filtration efficiency of 0.73 obtained from the study is extrapolated into a 24‐hour continuous arteriovenous hemofiltration performed at commonly used filtration rates (i.e., 6–12 ml/min), the 24‐hour hemofiltration clearances are estimated to range from 4 to 9 ml/min. These clearance values are found to correspond to only 10 to 25% of the mean total body clearance (about 35 ml/min) reported from anuric patients. Based upon the present findings coupled with the above‐assumed extrapolation, we recommend that no supplemental doses of famotidine be required for patients with renal failure during or after the intermittent or continuous (at least 24‐hour) arteriovenous hemofiltration.